IgM paraproteinaemic neuropathies

Abstract

To conduct a critical review of recent studies on the pathogenesis and treatment of IgM paraproteinaemic neuropathies and analyse their implication for patient management.A better definition and classification of IgM monoclonal gammopathies has led to recommendations on therapeutic strategies for these patients, particularly for those with the asymptomatic form of Waldenström macroglobulinemia. Studies on the pathogenetic role of IgM paraprotein in neuropathy have led to the identification of a novel antibody reactivity against trisulfated heparin disaccharide, which was associated with painful, predominantly sensory, axonal distal neuropathy. Pathological studies on patients with axonal polyneuropathy and no antibody reactivity of the IgM paraprotein have shown that vasculitis may play an important role in this form of neuropathy, as possibly confirmed by its positive response to steroids. A number of open pilot trials have addressed the effect in IgM paraproteinaemic neuropathies of the humanized monoclonal antibody (rituximab) directed against the CD20 antigen. Even if the results of these studies are less promising than initially hoped, they provide evidence that rituximab may be effective in some patients with this neuropathy.New insights into the pathogenesis of axonal forms of IgM paraproteinaemic neuropathy have derived from the identification of novel antibody reactivity and of vasculitis. The latter finding may justify the use of steroids, otherwise ineffective in IgM paraproteinaemic neuropathy. Rituximab has opened the way to more selective and apparently safer immune therapies for this neuropathy, but its efficacy needs to be confirmed by randomized controlled trials.